The use of immunotherapy treatment in malignant pheochromocytomas/paragangliomas: a case report

Abstract

Background Pheochromocytomas are a subset of paragangliomas, which are a rare group of neural crest cell-derived tumors. Malignant cases of both pheochromocytomas and paragangliomas are even rarer, and currently there is no standard of care. This case report details the use of off-label immunotherapy and its efficacy in the management of the aforementioned tumor. Case presentation Herein is presented a case of a 60-year-old Caucasian female with a rare malignant pheochromocytoma. The tumor was determined to be unresectable because of involvement of surrounding organs. Radiation therapy was also not a viable option because of concerns over appreciable toxicity in relation to mass size. As there is no standard of care for malignant cases, the patient was started on chemotherapeutic agents but was soon shown to be intolerant to this treatment. As she was ineligible for several clinical trials, the patient was started on the off-label immunotherapeutic agents nivolumab and ipilimumab. Immunotherapy use resulted in decreased tumor size, improved quality of life, and reconsideration for radiation therapy. Conclusions The use of immunotherapy in pheochromocytoma in this patient clearly demonstrated substantial benefit, as she was able to be reconsidered for radiation therapy. Not only has the patient been tolerant of this treatment, but she has exhibited progression-free survival of over 20 months. As there is no current standard treatment for malignant pheochromocytomas, the success of its use in this patient lends support to the ongoing clinical trials regarding the use of immunotherapy in rare tumors, including pheochromocytomas.

Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment

“…Other genes overexpressed in metastatic PCPG included genes associated with tissue remodeling and EMT, also consistent with a previous study 58 . Very low T cell infiltrates in most PCPG may predict limited benefit from immune checkpoint inhibitors, consistent with the modest responses to these drugs observed in PCPG patients to date 59 , 60 . Macrophages were abundant in PCPG but are highly heterogenous in their expression profile, with macrophage marker expression highest in PCPG tumors with neoangiogenic features, although not ubiquitous across all pseudohypoxic subtypes, including a significant fraction of the C1A ( SDHx ) group.…”

Immune Checkpoint Inhibitor Therapy in Neuroendocrine Tumors

“…However, the favorable treatment responses did not correlate with primary tumor PD-L1 positivity, hormonal status, hereditary syndrome status, or infiltrating mononuclear cells in the primary tumor. A combination therapy with ipilimumab and nivolumab used off-label in a 60-year-old patient with sporadic, metastatic, inoperable pheochromocytoma resulted in substantial reduction in tumor burden after close to 20 months of therapy 88 .…”